EnzymAgglo - Multiskalige modellgestützte Untersuchungen der Formation von katalytisch aktiven Clustern und Agglomeraten großer Multienzymkomplexe

Motivation

• Targeted formation of stable enzyme clusters and agglomerates is of highest interest for the construction of efficient and adjustable bioreaction cascades

• Nowadays no suitable methodology available to predict formation and stability of clusters and agglomerates

• Impact of process parameters – pH, temperature, mechanical stress – on cluster and aggregate formation and functionality yet hardly investigated

Objectives of this project:

• Identify mechanisms and determinants responsible for building functional and efficient agglomerates.

• Develop and validate solid model framework to describe and predict dynamic formation and reformation of multi-enzymatic complex clusters and agglomerates

• Influence of process conditions on formation and catalytic efficiency

Publikationen

• FEBS, Hrsg.: Full structural modeling of multi enzymatic nanomachines: flexible domain interactions within pyruvate dehydrogenase complex, 2017.
• Hezaveh S, Zeng A-P, Jandt U: Human Pyruvate Dehydrogenase Complex E2 and E3BP Core Subunits: New Models and Insights from Molecular Dynamics Simulations. Journal of Physical Chemistry B(120): S. 4399–4409, 2016.
• Samira Hezaveh, An-Ping Zeng, and Uwe Jandt : Investigation of Core Structure and Stability of Human Pyruvate Dehydrogenase Complex: a Coarse-Grained Approach. ACS Omega, 2(3): S. 1134-1145, 2017.
• U. Jandt, S. Hezaveh, S. Ilhan, J. Guo, J. Tatur, G. Fuge: Modellierung und Modifikation von Multienzymkomplexen: Neue Strategien und Prozesse. Tagungsband 18. Heiligenstädter Kolloquium: S. 279-286, 2016. ISBN 978-3-00-054165-0.
• Jin Guo, Samira Hezaveh, Jana Tatur, An-Ping Zeng, Uwe Jandt: Reengineering of human pyruvate dehydrogenase complex: from disintegration to highly active agglomerates. Biochemical Journal, 474(5): S. 865-875, 2017. , DOI: 10.1042/BCJ20160916
• Hezaveh, Samira and Zeng, An-Ping and Jandt, Uwe: Full Enzyme Complex Simulation: Interactions in Human Pyruvate Dehydrogenase Complex. Journal of chemical information and modeling, 58(2): S. 362--369, 2018. , DOI: 10.1021/acs.jcim.7b00557
• Depta P.N., Jandt U., Dosta M., Zeng A.-P., Heinrich S.: Towards multi-scale modeling of proteins and bio-agglomerates: An orientation-sensitive diffusion model for the integration of Molecular Dynamics and the Discrete Element Method.. J. Chem. Inf. Model., 2018. , DOI: 10.1021/acs.jcim.8b00613
• Depta P.N., Jandt U., Ilhan S., Müller C., Dosta M., Zeng A.-P., Heinrich S.: Multiscale modeling to investigate catalytically active enzymatic aggregates for cascade bioreactions. 2018. , DOI: 10.1002/cite.201855443CIT, 90: 1338-1338.
• Ilhan S., Müller C., Jandt U.: Dynamics of a sub‐unit assembly within multienzyme complex and its mutants. []. , DOI: 10.1002/cite.201855325CIT, 90: 1280-1280.